Research Summary

Michelle's lab develops innovative approaches to screen for chemical tools and drug leads, using biophysical approaches like fragment-based drug discovery and biological approaches including high-content imaging with primary cells and organisms. Our goal is to demonstrate 'druggability' of new target classes and to use our compounds to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is co-Director of the Small Molecule Discovery Center, a collaborative research facility that includes high-throughput screening and medicinal chemistry (smdc.ucsf.edu). The SMDC is a Cancer Center Core.

Research Funding

  • July 1, 2020 - June 30, 2024 - Discovery of Small Molecule Ligands for PHD1 Reader Domain of Histone Demethylase KDM5A, Co-Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA250459
  • September 5, 2018 - July 31, 2022 - Protein and small-molecule tools to probe the conformational dependence of the VCP/p97 protein-protein interaction network, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01GM130145
  • March 23, 2016 - February 29, 2020 - A high content screen dissecting ciliogenesis and oncogenic Hedgehog signaling, Co-Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA181231
  • September 30, 2013 - June 30, 2018 - Translational Studies Linking Aging and Cancer, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01AG044515

Education

1990, Bryn Mawr College, Bryn Mawr, PA, B.A., Chemistry
1997, California Institute of Technology, Pasadena, CA, Ph.D., Chemistry
1999, Genentech, Inc, South San Francisco, CA and Sunesis Pharmaceuticals, Redwood City, CA, Postdoctoral fellowship, Protein Engineering

Honors & Awards

  • 1991
    European Traveling Fellowship, Bryn Mawr College
  • 1991-1992
    Blodgett Fellowship, General Electric Foundation
  • 1992-1995
    National Science Foundation Predoctoral Fellowship
  • 1995-1997
    National Institutes of Health Traineeship
  • 1997-1999
    Daymon Runyon-Walter Winchell Cancer Research Postdoctoral Fellowship
  • 2010
    Keynote address, Drug Discovery Chemistry, Protein-Protein Interactions (San Diego)
  • 2012
    Keynote speaker, EFMC-ISMC (Berlin)
  • 2013
    Keynote speaker, PPI-NET (London)
  • 2013
    Finalist, SLAS Innovation Award

Selected Publications

  1. Eline Sijbesma, Kenneth K. Hallenbeck, Sebastian A. Andrei, Reanne R. Rust, Joris M. C. Adriaans, Luc Brunsveld, Michelle R. Arkin, Christian Ottmann Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers.  View on PubMed
  2. Espinosa JA, Pohan G, Arkin MR, Markossian S Real-Time Assessment of Mitochondrial Toxicity in HepG2 Cells Using the Seahorse Extracellular Flux Analyzer.  View on PubMed
  3. Chin MY, Espinosa JA, Pohan G, Markossian S, Arkin MR Reimagining dots and dashes: visualizing structure and function of organelles for high-content imaging analysis.  View on PubMed
  4. Tyagi R, Bulman CA, Cho-Ngwa F, Fischer C, Marcellino C, Arkin MR, McKerrow JH, McNamara CW, Mahoney M, Tricoche N, Jawahar S, Janetka JW, Lustigman S, Sakanari J, Mitreva M An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease.  View on PubMed
  5. Chen S, Suzuki BM, Dohrmann J, Singh R, Arkin MR, Caffrey CR A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery.  View on PubMed
  6. Antonia MH Piergies, Panos Theofilas, Cathrine Petersen, Alexander J Ehrenberg, Song Li, Dulce Ovando Morales, Rana A Eser, Teddy Yang, Shireen Khan, Brian Chin, Raymond Ng, Michelle Arkin, Lea Tenenholz Grinberg Caspase-6-mediated tau cleavage and pathology in Alzheimer’s disease and other tauopathies.  View on PubMed
  7. Pohan G, Espinosa JA, Chen S, Ang KK, Arkin MR, Markossian S Multiparametric High-Content Assays to Measure Cell Health and Oxidative Damage as a Model for Drug-Induced Liver Injury.  View on PubMed
  8. Sijbesma E, Somsen BA, Miley GP, Leijten-van de Gevel IA, Brunsveld L, Arkin MR, Ottmann C Fluorescence Anisotropy-Based Tethering for Discovery of Protein-Protein Interaction Stabilizers.  View on PubMed
  9. Abdel Aziz MH, Fan Y, Liu L, Moasser MM, Fu H, Jura N, Arkin MR Expression and purification of active human kinases using Pichia pastoris as a general-purpose host.  View on PubMed
  10. Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Coronado PER, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K Author Correction: Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation.  View on PubMed
  11. Blay V, Tolani B, Ho SP, Arkin MR High-Throughput Screening: today's biochemical and cell-based approaches.  View on PubMed
  12. Leandro J, Khamrui S, Wang H, Suebsuwong C, Nemeria NS, Huynh K, Moustakim M, Secor C, Wang M, Dodatko T, Stauffer B, Wilson CG, Yu C, Arkin MR, Jordan F, Sanchez R, DeVita RJ, Lazarus MB, Houten SM Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex.  View on PubMed
  13. Guillory X, Wolter M, Leysen S, Neves JF, Kuusk A, Genet S, Somsen B, Morrow JK, Rivers E, van Beek L, Patel J, Goodnow R, Schoenherr H, Fuller N, Cao Q, Doveston RG, Brunsveld L, Arkin MR, Castaldi P, Boyd H, Landrieu I, Chen H, Ottmann C Fragment-based Differential Targeting of PPI Stabilizer Interfaces.  View on PubMed
  14. Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Rios Coronado PE, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation.  View on PubMed
  15. Zhang P, Zhai Y, Cregg J, Ang KK, Arkin M, Kenyon C Stress Resistance Screen in a Human Primary Cell Line Identifies Small Molecules That Affect Aging Pathways and Extend Caenorhabditis elegans' Lifespan.  View on PubMed
  16. Chen X, Li Y, Wang C, Tang Y, Mok SA, Tsai RM, Rojas JC, Karydas A, Miller BL, Boxer AL, Gestwicki JE, Arkin M, Cuervo AM, Gan L Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.  View on PubMed
  17. Chris G.M. Wilson, Michelle R. Arkin Chapter 5 Screening and biophysics in small molecule discovery.  View on PubMed
  18. Sanchez MI, de Vries LE, Lehmann C, Lee JT, Ang KK, Wilson C, Chen S, Arkin MR, Bogyo M, Deu E Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors by high throughput screening.  View on PubMed
  19. Walhart T, Isaacson-Wechsler E, Ang KH, Arkin M, Tugizov S, Palefsky JM A Cell-Based Renilla Luminescence Reporter Plasmid Assay for High-Throughput Screening to Identify Novel FDA-Approved Drug Inhibitors of HPV-16 Infection.  View on PubMed
  20. Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.  View on PubMed

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